Prognostic factors and nomogram construction for primary retroperitoneal myxoid/round cell liposarcoma: an analysis of population-based data
Background: It has been reported that the prognosis for myxoid/round cell liposarcoma (MLPS/RCLPS) is inconsistent across different sites. However, there are neither prognostic studies nor predictive models that focused on MLPS/RCLPS of retroperitoneal origin.
Methods: Utilizing the Surveillance, Epidemiology, and End Results database, we selected 171 primary retroperitoneal MLPS/RCLPS cases from the period between 2000 and 2019. Prognostic factors influencing disease-specific survival were identified through Cox regression analysis. These independent prognostic factors were then used to construct a DSS nomogram prediction model. The accuracy and reliability of this nomogram were evaluated using the concordance index (C-index) and calibration plots. Furthermore, we categorized patient prognosis using an X-tile based on the nomogram score.
Results: The observed 5-year and 10-year DSS rates for all patients were 64.0% (95% CI: 56.2% – 71.8%) and 47.1% (95% CI: 38.1% – 56.1%), respectively. The patient cohort had a median age of 64 years, ranging from 24 to 92 years, with a slight male predominance (n = 92, 53.8%) over females (n = 79, 46.2%). Distant metastases were diagnosed in 24 patients (14%). The distribution of MLPS and RCLPS was 89.5% and 10.5%, respectively. In terms of treatment, adjuvant radiotherapy was administered to 33 patients (19.3%), neoadjuvant radiotherapy to 9 patients (5.3%), and chemotherapy to 20 patients (11.7%), while a significant majority (83.6%) underwent surgical procedures. Independent prognostic factors for DSS included age (HR = 1.039, P < 0.001), marital status (P = 0.029), history of previous tumors (HR = 0.257, P = 0.007), presence of metastatic disease (HR = 2.206, P = 0.027), and surgical treatment (HR = 0.490, P = 0.036). A nomogram prediction model was constructed to forecast 1-, 5-, and 10-year DSS rates, with a C-index of 0.739. Calibration plots demonstrated a strong correlation between the nomogram’s predictions and actual observations. Based on the prediction model, patients were stratified into three groups, and significant differences in prognosis were observed between these groups.
Conclusion: A poorer prognosis is associated with retroperitoneal-derived MLPS/RCLPS than with other sites. The nomogram prediction model we built can be used to assist patients in consulting with their doctors and selecting patients for clinical trials.
Relevance for Patients: Our study highlights the unique challenges and prognosis variations in retroperitoneal myxoid/RCLPS. The developed nomogram serves as a valuable tool for patients, aiding informed discussions with doctors and guiding decisions on treatment and clinical trial participation.
[1] Doyle LA. Sarcoma Classification: An Update Based on the 2013 World Health Organization Classification of Tumors of Soft Tissue and Bone. Cancer 2014;120:1763-1774. doi: 10.1002/cncr.28657
[2] Setsu N, Miyake M, Wakai S, Nakatani F, Kobayashi E, Chuman H, et al. Primary Retroperitoneal Myxoid Liposarcomas. Am J Surg Pathol 2016;40:1286-90. doi: 10.1097/PAS.0000000000000657
[3] Zhuang A, Zhuang A, Wu Q, Lu W, Tong H, Zhang Y. Prognostic Factor Analysis and Nomogram Construction of Primary Retroperitoneal Liposarcoma: A Review of 10 Years of Treatment Experience in a Single Asian Cohort of 211 Cases. Front Oncol 2021;11:777647. doi: 10.3389/fonc.2021.777647
[4] Kilpatrick SE, Doyon J, Choong PF, Sim FH, Nascimento AG. The Clinicopathologic Spectrum of Myxoid and Round Cell Liposarcoma. A Study of 95 Cases. Cancer 1996;77:1450-8. doi: 10.1002/(SICI)1097-0142(19960415)77:8<1450::AIDCNCR5>3.0.CO;2-G
[5] Alaggio R, Coffin CM, Weiss SW, Bridge JA, Issakov J, Oliveira AM, et al. Liposarcomas in Young Patients: A Study of 82 Cases Occurring in Patients Younger than 22 Years of Age. Am J Surg Pathol 2009;33:645-58. doi: 10.1097/PAS.0b013e3181963c9c
[6] Dei TA. Liposarcomas: Diagnostic Pitfalls and New Insights. Histopathology 2014;64:38-52. doi: 10.1111/his.12311
[7] Abaricia S, Hirbe AC. Diagnosis and Treatment of Myxoid Liposarcomas: Histology Matters. Curr Treat Options Oncol 2018;19:64. doi: 10.1007/s11864-018-0590-5
[8] Panagopoulos I, Mandahl N, Ron D, Hoglund M, Nilbert M, Mertens F, et al. Characterization of the CHOP Breakpoints and Fusion Transcripts in Myxoid Liposarcomas with the 12;16 Translocation. Cancer Res 1994;54:6500-3.
[9] Knight JC, Renwick PJ, Dal Cin P, Van den Berghe H, Fletcher CD. Translocation t(12;16)(q13;p11) in Myxoid Liposarcoma and Round Cell Liposarcoma: Molecular and Cytogenetic Analysis. Cancer Res 1995;55:24-7.
[10] Fiore M, Grosso F, Lo VS, Pennacchioli E, Stacchiotti S, Ferrari A, et al. Myxoid/Round Cell and Pleomorphic Liposarcomas: Prognostic Factors and Survival in a Series of Patients Treated at a Single Institution. Cancer 2007;109:2522-31. doi: 10.1002/cncr.22720
[11] Spillane AJ, Fisher C, Thomas JM. Myxoid Liposarcoma--the Frequency and the Natural History of Nonpulmonary Soft Tissue Metastases. Ann Surg Oncol 1999;6:389-94. doi: 10.1007/s10434-999-0389-5
[12] Estourgie SH, Nielsen GP, Ott MJ. Metastatic Patterns of Extremity Myxoid Liposarcoma and their Outcome. J Surg Oncol 2002;80:89-93. doi: 10.1002/jso.10093
[13] Pitson G, Robinson P, Wilke D, Kandel RA, White L, Griffin AM, et al. Radiation Response: An Additional Unique Signature of Myxoid Liposarcoma. Int J Radiat Oncol Biol Phys 2004;60:522-6. doi: 10.1016/j.ijrobp.2004.03.009
[14] Vijay A, Ram L. Retroperitoneal Liposarcoma: AComprehensive Review. Am J Clin Oncol 2015;38:213-9. doi: 10.1097/COC.0b013e31829b5667
[15] Lou Y, Ma Y, Li H, Song Y, Zhang X, Lin H, et al. High Expression of Fibroblast Growth Factor-21 in Liposarcoma Patients Indicated Better Prognosis and Less Recurrence. Biochem Biophys Res Commun 2018;503:1130-3. doi: 10.1016/j.bbrc.2018.06.130
[16] Perrone F, Tamborini E, Suardi S, Lagonigro MS, Pilotti S. Re: Oda et al. Frequent Alteration of p16INK4a/p14ARF and p53 Pathways in the Round Cell Component of Myxoid/Round Cell Liposarcoma: p53 Gene Alterations and Reduced p14ARF Expression Both Correlate withpoor prognosis. J Pathol 2005;207:410-21. J Pathol 2006;209:281, 282. doi: 10.1002/path.1994
[17] Kim JH, Lee JS, Kim EJ, Park KH, Kim KH, Yi SY, et al. Prognostic Implications of PIK3CA Amplification in Curatively Resected Liposarcoma. Oncotarget 2016;7:24549-58. doi: 10.18632/oncotarget.8240
[18] Iura K, Kohashi K, Hotokebuchi Y, Ishii T, Maekawa A, Yamada Y, et al. Cancer-testis Antigens PRAME and NYESO-1 Correlate with Tumour Grade and poor Prognosis in Myxoid Liposarcoma. J Pathol Clin Res 2015;1:144-59. doi: 10.1002/cjp2.16
[19] Wu H, Zhang Q, Zhao Y, Xu F, Zhang J, He H, et al. Association of Sirtuin-1 and Vascular Endothelial Growth Factor Expression with Tumor Progression and Poor Prognosis in Liposarcoma. J Int Med Res 2020;48:0300060520926355. doi: 10.1177/0300060520926355
[20] Kunstlinger H, Fassunke J, Schildhaus HU, Brors B, HeydtC, Ihle MA, et al. FGFR2 is Overexpressed in Myxoid Liposarcoma and Inhibition of FGFR Signaling Impairs Tumor Growth in vitro. Oncotarget 2015;6:20215-30. doi: 10.18632/oncotarget.4046
[21] Guadagnolo BA, Zagars GK, Ballo MT, Patel SR, Lewis VO, Benjamin RS, et al. Excellent Local Control Rates and Distinctive Patterns of Failure in Myxoid Liposarcoma Treated with Conservation Surgery and Radiotherapy. Int J Radiat Oncol Biol Phys 2008;70:760-5. doi: 10.1016/j.ijrobp.2007.07.2337
[22] Moreau LC, Turcotte R, Ferguson P, Wunder J, Clarkson P, Masri B, et al. Myxoid\Round Cell Liposarcoma (MRCLS) Revisited: An Analysis of 418 Primarily Managed Cases. Ann Surg Oncol 2012;19:1081-8. doi: 10.1245/s10434-011-2127-z
[23] Singer S, Antonescu CR, Riedel E, Brennan MF. Histologic Subtype and Margin of Resection Predict Pattern of Recurrence and Survival for Retroperitoneal Liposarcoma. Ann Surg 2003;238:358-70, 370-1. doi: 10.1097/01.sla.0000086542.11899.38
[24] Durr HR, Rauh J, Baur-Melnyk A, Knosel T, Lindner L, Roeder F, et al. Myxoid Liposarcoma: Local Relapse and Metastatic Pattern in 43 Patients. BMC Cancer 2018;18:304. doi: 10.1186/s12885-018-4226-8
[25] Chowdhry V, Goldberg S, DeLaney TF, Cote GM, Chebib I, Kim J, et al. Myxoid Liposarcoma: Treatment Outcomes from Chemotherapy and Radiation Therapy. Sarcoma 2018;2018:8029157. doi: 10.1155/2018/8029157
[26] Lansu J, Bovee J, Braam P, van Boven H, Flucke U, Bonenkamp JJ, et al. Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial. JAMA Oncol 2021;7:e205865. doi: 10.1001/jamaoncol.2020.5865
[27] Gronchi A, Strauss DC, Miceli R, Bonvalot S, Swallow CJ, Hohenberger P, et al. Variability in Patterns of Recurrence After Resection of Primary Retroperitoneal Sarcoma (RPS): A Report on 1007 Patients from the Multiinstitutional Collaborative RPS Working Group. Ann Surg 2016;263:1002-9. doi: 10.1097/SLA.0000000000001447
[28] Dalal KM, Kattan MW, Antonescu CR, Brennan MF, Singer S. Subtype Specific Prognostic Nomogram for Patients with Primary Liposarcoma of the Retroperitoneum, Extremity, or Trunk. Ann Surg 2006;244:381-91. doi: 10.1097/01.sla.0000234795.98607.00
[29] Gronchi A, Miceli R, Shurell E, Eilber FC, Eilber FR, Anaya DA, et al. Outcome Prediction in Primary Resected Retroperitoneal Soft Tissue Sarcoma: Histology-specific Overall Survival and Disease-free Survival Nomograms Built on Major Sarcoma Center Data Sets. J Clin Oncol 2013;31:1649-55. doi: 10.1200/JCO.2012.44.3747
[30] Tan MC, Brennan MF, Kuk D, Agaram NP, Antonescu CR, Qin LX, et al. Histology-based Classification Predicts Pattern of Recurrence and Improves Risk Stratification in Primary Retroperitoneal Sarcoma. Ann Surg 2016;263:593-600. doi: 10.1097/SLA.0000000000001149
[31] Krajc K, Mirosevic S, Sajovic J, Klemenc KZ, Spiegel D, Drevensek G, et al. Marital Status and Survival in Cancer Patients: A Systematic Review and Meta-analysis. Cancer Med 2023;12:1685-708. doi: 10.1002/cam4.5003
[32] Aizer AA, Chen MH, McCarthy EP, Mendu ML, Koo S, Wilhite TJ, et al. Marital Status and Survival in Patients with Cancer. J Clin Oncol 2013;31:3869-76. doi: 10.1200/JCO.2013.49.6489
[33] Irwin M, Daniels M, Smith TL, Bloom E, Weiner H. Impaired Natural Killer Cell Activity during Bereavement. Brain Behav Immun 1987;1:98-104. doi: 10.1016/0889-1591(87)90011-0
[34] Dopp JM, Miller GE, Myers HF, Fahey JL. Increased Natural Killer-Cell Mobilization and Cytotoxicity during Marital Conflict. Brain Behav Immun 2000;14:10-26. doi: 10.1006/brbi.1999.0567
[35] Chen ZH, Yang KB, Zhang YZ, Wu CF, Wen DW, Lv JW, et al. Assessment of Modifiable Factors for the Association of Marital Status with Cancer-Specific Survival. JAMA Netw Open 2021;4:e2111813. doi: 10.1001/jamanetworkopen.2021.11813
[36] Alamanda VK, Song Y, Holt GE. Effect of Marital Status on Treatment and Survival of Extremity Soft Tissue Sarcoma. Ann Oncol 2014;25:725-9. doi: 10.1093/annonc/mdt583
[37] Zhang SL, Wang WR, Liu ZJ, Wang ZM. Marital Status and Survival in Patients with Soft Tissue Sarcoma: A Population-based, Propensity-Matched Study. Cancer Med 2019;8:465-79. doi: 10.1002/cam4.1802
[38] Kobayashi E, Kawai A. Histology-specific Chemotherapy in Soft-Tissue Sarcomas. Gan To Kagaku Ryoho 2017;44:468-72.
[39] Nassif EF, Keung EZ, Thirasastr P, Somaiah N. Myxoid Liposarcomas: Systemic Treatment Options. Curr Treat Options Oncol 2023;24:274-91. doi: 10.1007/s11864-023-01057-4
[40] Nakamura T, Sudo A. The Role of Trabectedin in Soft Tissue Sarcoma. Front Pharmacol 2022;13:777872. doi: 10.3389/fphar.2022.777872
[41] Kim CG, Sim NS, Kim JE, Yun KH, Lee YH, Kim SH, et al. Phase II Clinical Trial of Eribulin-Gemcitabine Combination Therapy in Previously Treated Patients with Advanced Liposarcoma or Leiomyosarcoma. Clin Cancer Res 2022;28:3225-34. doi: 10.1158/1078-0432.CCR-22-0518
[42] Schoffski P. Established and Experimental SystemicTreatment Options for Advanced Liposarcoma. Oncol Res Treat 2022;45:525-43. doi: 10.1159/000524939
[43] Salduz A, Alpan B, Valiyev N, Ozmen E, Iribas A, Agaoglu F, et al. Neoadjuvant Radiotherapy for Myxoid Liposarcomas: Oncologic Outcomes and Histopathologic Correlations. Acta Orthop Traumatol Turc 2017;51:355-61. doi: 10.1016/j.aott.2017.03.009
[44] von Mehren M, Kane JM, Agulnik M, Bui MM, CarrAscher J, Choy E, et al. Soft Tissue Sarcoma, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2022;20:815-33. doi: 10.6004/jnccn.2022.0035
[45] Bonvalot S, Gronchi A, Le Pechoux C, Swallow CJ, Strauss D, Meeus P, et al. Preoperative Radiotherapy Plus Surgery Versus Surgery Alone for Patients with Primary Retroperitoneal Sarcoma (EORTC-62092: STRASS): A Multicentre, Open-Label, Randomised, Phase 3 Trial. Lancet Oncol 2020;21:1366-77. doi: 10.1016/S1470-2045(20)30446-0
[46] Lee LH, Tepper S, Owen G, Wang D, Lopez-Hisijos N, Colman MW, et al. Radiotherapy, Volume Reduction, and Short-term Surgical Outcomes in the Treatment of Large Myxoid Liposarcomas. Radiat Oncol J 2022;40:172-9. doi: 10.3857/roj.2022.00094